Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL
Authorized Users Only
2021
Authors
Agathangelidis, AndreasChatzidimitriou, Anastasia
Gemenetzi, Katerina
Giudicelli, Veronique
Karypidou, Maria
Plevova, Karla
Davis, Zadie
Yan, Xiao-Jie
Jeromin, Sabine
Schneider, Christof
Pedersen, Lone Bredo
Tschumper, Renee C.
Sutton, Lesley-Ann
Baliakas, Panagiotis
Scarfo, Lydia
van Gastel, Ellen J.
Armand, Marine
Tausch, Eugen
Biderman, Bella
Baer, Constance
Bagnara, Davide
Navarro, Alba
de Septenville, Anne Langlois
Guido, Valentina
Mitterbauer-Hohendanner, Gerlinde
Dimovski, Aleksandar
Brieghel, Christian
Lawless, Sarah
Meggendorfer, Manja
Brazdilova, Kamila
Ritgen, Matthias
Facco, Monica
Tresoldi, Cristina
Visentin, Andrea
Patriarca, Andrea
Catherwood, Mark
Bonello, Lisa
Sudarikov, Andrey
Vanura, Katrina
Roumelioti, Maria
Francova, Hana Skuhrova
Moysiadis, Theodoros
Veronese, Silvio
Giannopoulos, Krzysztof
Mansouri, Larry
Karan-Đurašević, Teodora
Sandaltzopoulos, Raphael
Bodor, Csaba
Fais, Franco
Kater, Arnon
Panovska, Irina
Rossi, Davide
Alshemmari, Salem
Panagiotidis, Panagiotis
Costeas, Paul
Espinet, Blanca
Antić, Darko
Foroni, Letizia
Montillo, Marco
Trentin, Livio
Stavroyianni, Niki
Gaidano, Gianluca
di Celle, Paola Francia
Niemann, Carsten
Campo, Elias
Anagnostopoulos, Achilles
Pott, Christiane
Fischer, Kirsten
Hallek, Michael
Oscier, David
Stilgenbauer, Stephan
Haferlach, Claudia
Jelinek, Diane
Chiorazzi, Nicholas
Pospisilova, Sarka
Lefranc, Marie-Paule
Kossida, Sofia
Langerak, Anton W.
Belessi, Chrysoula
Davi, Frederic
Rosenquist, Richard
Ghia, Paolo
Stamatopoulos, Kostas
Article (Published version)
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Show full item recordAbstract
Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size an...d ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed "satellites," were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL.
Source:
Blood, 2021, 137, 10, 1365-1376Publisher:
- Amer Soc Hematology, Washington
Funding / projects:
- Hellenic Foundation for Research and Innovation (HFRI)
- General Secretariat for Research and Technology (GSRT) [336]
- Hellenic Precision Medicine Network in Oncology
- Swedish Cancer Society
- Swedish Research Council
- Knut and Alice Wallenberg Foundation
- Karolinska Institutet
- Karolinska University Hospital
- Radiumhemmets Forskningsfonder, Stockholm
- German Research Foundation (DFG) [SFB1074]
- Bournemouth Leukaemia Fund
- Kuwait Foundation for Advancement of Sciences (KFAS) [PR1713MM03]
- Polish Scientific Centre [NCN 2018/29/B/NZ5/02706]
- Swiss Cancer League [3746, 4395 4660, 4705]
- European Research Council (ERC) Consolidator Grant CLLCLONE [772051]
- Swiss National Science Foundation, Bern, Switzerland [320030_169670/1, 310030_192439]
- Leukemia & Lymphoma Society, Translational Research Program [6594-20]
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG 15426]
- European Union [794075]
- Momentum Grant of the Hungarian Academy of Sciences [LP-95021]
- Hungarian National Research, Development and Innovation Office [NVKP_16-1-2016-0004]
- Leukaemia and Lymphoma Northern Ireland (NI)
- AIRC Milan Project [IG 15397]
- Project NPUII MEYSCZ [CEITEC2020 LQ1601]
- University Hospital Brno Project [MH-CZ RVO 65269705]
- AIRC [21198]
- Novo Nordisk Foundation [NNF16OC0019302]
- MH-CZ AZV [NV19-03-00091]
DOI: 10.1182/blood.2020007039
ISSN: 0006-4971
PubMed: 32992344
WoS: 000646099500016
Scopus: 2-s2.0-85102607193
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Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Agathangelidis, Andreas AU - Chatzidimitriou, Anastasia AU - Gemenetzi, Katerina AU - Giudicelli, Veronique AU - Karypidou, Maria AU - Plevova, Karla AU - Davis, Zadie AU - Yan, Xiao-Jie AU - Jeromin, Sabine AU - Schneider, Christof AU - Pedersen, Lone Bredo AU - Tschumper, Renee C. AU - Sutton, Lesley-Ann AU - Baliakas, Panagiotis AU - Scarfo, Lydia AU - van Gastel, Ellen J. AU - Armand, Marine AU - Tausch, Eugen AU - Biderman, Bella AU - Baer, Constance AU - Bagnara, Davide AU - Navarro, Alba AU - de Septenville, Anne Langlois AU - Guido, Valentina AU - Mitterbauer-Hohendanner, Gerlinde AU - Dimovski, Aleksandar AU - Brieghel, Christian AU - Lawless, Sarah AU - Meggendorfer, Manja AU - Brazdilova, Kamila AU - Ritgen, Matthias AU - Facco, Monica AU - Tresoldi, Cristina AU - Visentin, Andrea AU - Patriarca, Andrea AU - Catherwood, Mark AU - Bonello, Lisa AU - Sudarikov, Andrey AU - Vanura, Katrina AU - Roumelioti, Maria AU - Francova, Hana Skuhrova AU - Moysiadis, Theodoros AU - Veronese, Silvio AU - Giannopoulos, Krzysztof AU - Mansouri, Larry AU - Karan-Đurašević, Teodora AU - Sandaltzopoulos, Raphael AU - Bodor, Csaba AU - Fais, Franco AU - Kater, Arnon AU - Panovska, Irina AU - Rossi, Davide AU - Alshemmari, Salem AU - Panagiotidis, Panagiotis AU - Costeas, Paul AU - Espinet, Blanca AU - Antić, Darko AU - Foroni, Letizia AU - Montillo, Marco AU - Trentin, Livio AU - Stavroyianni, Niki AU - Gaidano, Gianluca AU - di Celle, Paola Francia AU - Niemann, Carsten AU - Campo, Elias AU - Anagnostopoulos, Achilles AU - Pott, Christiane AU - Fischer, Kirsten AU - Hallek, Michael AU - Oscier, David AU - Stilgenbauer, Stephan AU - Haferlach, Claudia AU - Jelinek, Diane AU - Chiorazzi, Nicholas AU - Pospisilova, Sarka AU - Lefranc, Marie-Paule AU - Kossida, Sofia AU - Langerak, Anton W. AU - Belessi, Chrysoula AU - Davi, Frederic AU - Rosenquist, Richard AU - Ghia, Paolo AU - Stamatopoulos, Kostas PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1427 AB - Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed "satellites," were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL. PB - Amer Soc Hematology, Washington T2 - Blood T1 - Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL EP - 1376 IS - 10 SP - 1365 VL - 137 DO - 10.1182/blood.2020007039 ER -
@article{ author = "Agathangelidis, Andreas and Chatzidimitriou, Anastasia and Gemenetzi, Katerina and Giudicelli, Veronique and Karypidou, Maria and Plevova, Karla and Davis, Zadie and Yan, Xiao-Jie and Jeromin, Sabine and Schneider, Christof and Pedersen, Lone Bredo and Tschumper, Renee C. and Sutton, Lesley-Ann and Baliakas, Panagiotis and Scarfo, Lydia and van Gastel, Ellen J. and Armand, Marine and Tausch, Eugen and Biderman, Bella and Baer, Constance and Bagnara, Davide and Navarro, Alba and de Septenville, Anne Langlois and Guido, Valentina and Mitterbauer-Hohendanner, Gerlinde and Dimovski, Aleksandar and Brieghel, Christian and Lawless, Sarah and Meggendorfer, Manja and Brazdilova, Kamila and Ritgen, Matthias and Facco, Monica and Tresoldi, Cristina and Visentin, Andrea and Patriarca, Andrea and Catherwood, Mark and Bonello, Lisa and Sudarikov, Andrey and Vanura, Katrina and Roumelioti, Maria and Francova, Hana Skuhrova and Moysiadis, Theodoros and Veronese, Silvio and Giannopoulos, Krzysztof and Mansouri, Larry and Karan-Đurašević, Teodora and Sandaltzopoulos, Raphael and Bodor, Csaba and Fais, Franco and Kater, Arnon and Panovska, Irina and Rossi, Davide and Alshemmari, Salem and Panagiotidis, Panagiotis and Costeas, Paul and Espinet, Blanca and Antić, Darko and Foroni, Letizia and Montillo, Marco and Trentin, Livio and Stavroyianni, Niki and Gaidano, Gianluca and di Celle, Paola Francia and Niemann, Carsten and Campo, Elias and Anagnostopoulos, Achilles and Pott, Christiane and Fischer, Kirsten and Hallek, Michael and Oscier, David and Stilgenbauer, Stephan and Haferlach, Claudia and Jelinek, Diane and Chiorazzi, Nicholas and Pospisilova, Sarka and Lefranc, Marie-Paule and Kossida, Sofia and Langerak, Anton W. and Belessi, Chrysoula and Davi, Frederic and Rosenquist, Richard and Ghia, Paolo and Stamatopoulos, Kostas", year = "2021", abstract = "Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed "satellites," were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL.", publisher = "Amer Soc Hematology, Washington", journal = "Blood", title = "Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL", pages = "1376-1365", number = "10", volume = "137", doi = "10.1182/blood.2020007039" }
Agathangelidis, A., Chatzidimitriou, A., Gemenetzi, K., Giudicelli, V., Karypidou, M., Plevova, K., Davis, Z., Yan, X., Jeromin, S., Schneider, C., Pedersen, L. B., Tschumper, R. C., Sutton, L., Baliakas, P., Scarfo, L., van Gastel, E. J., Armand, M., Tausch, E., Biderman, B., Baer, C., Bagnara, D., Navarro, A., de Septenville, A. L., Guido, V., Mitterbauer-Hohendanner, G., Dimovski, A., Brieghel, C., Lawless, S., Meggendorfer, M., Brazdilova, K., Ritgen, M., Facco, M., Tresoldi, C., Visentin, A., Patriarca, A., Catherwood, M., Bonello, L., Sudarikov, A., Vanura, K., Roumelioti, M., Francova, H. S., Moysiadis, T., Veronese, S., Giannopoulos, K., Mansouri, L., Karan-Đurašević, T., Sandaltzopoulos, R., Bodor, C., Fais, F., Kater, A., Panovska, I., Rossi, D., Alshemmari, S., Panagiotidis, P., Costeas, P., Espinet, B., Antić, D., Foroni, L., Montillo, M., Trentin, L., Stavroyianni, N., Gaidano, G., di Celle, P. F., Niemann, C., Campo, E., Anagnostopoulos, A., Pott, C., Fischer, K., Hallek, M., Oscier, D., Stilgenbauer, S., Haferlach, C., Jelinek, D., Chiorazzi, N., Pospisilova, S., Lefranc, M., Kossida, S., Langerak, A. W., Belessi, C., Davi, F., Rosenquist, R., Ghia, P.,& Stamatopoulos, K.. (2021). Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. in Blood Amer Soc Hematology, Washington., 137(10), 1365-1376. https://doi.org/10.1182/blood.2020007039
Agathangelidis A, Chatzidimitriou A, Gemenetzi K, Giudicelli V, Karypidou M, Plevova K, Davis Z, Yan X, Jeromin S, Schneider C, Pedersen LB, Tschumper RC, Sutton L, Baliakas P, Scarfo L, van Gastel EJ, Armand M, Tausch E, Biderman B, Baer C, Bagnara D, Navarro A, de Septenville AL, Guido V, Mitterbauer-Hohendanner G, Dimovski A, Brieghel C, Lawless S, Meggendorfer M, Brazdilova K, Ritgen M, Facco M, Tresoldi C, Visentin A, Patriarca A, Catherwood M, Bonello L, Sudarikov A, Vanura K, Roumelioti M, Francova HS, Moysiadis T, Veronese S, Giannopoulos K, Mansouri L, Karan-Đurašević T, Sandaltzopoulos R, Bodor C, Fais F, Kater A, Panovska I, Rossi D, Alshemmari S, Panagiotidis P, Costeas P, Espinet B, Antić D, Foroni L, Montillo M, Trentin L, Stavroyianni N, Gaidano G, di Celle PF, Niemann C, Campo E, Anagnostopoulos A, Pott C, Fischer K, Hallek M, Oscier D, Stilgenbauer S, Haferlach C, Jelinek D, Chiorazzi N, Pospisilova S, Lefranc M, Kossida S, Langerak AW, Belessi C, Davi F, Rosenquist R, Ghia P, Stamatopoulos K. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. in Blood. 2021;137(10):1365-1376. doi:10.1182/blood.2020007039 .
Agathangelidis, Andreas, Chatzidimitriou, Anastasia, Gemenetzi, Katerina, Giudicelli, Veronique, Karypidou, Maria, Plevova, Karla, Davis, Zadie, Yan, Xiao-Jie, Jeromin, Sabine, Schneider, Christof, Pedersen, Lone Bredo, Tschumper, Renee C., Sutton, Lesley-Ann, Baliakas, Panagiotis, Scarfo, Lydia, van Gastel, Ellen J., Armand, Marine, Tausch, Eugen, Biderman, Bella, Baer, Constance, Bagnara, Davide, Navarro, Alba, de Septenville, Anne Langlois, Guido, Valentina, Mitterbauer-Hohendanner, Gerlinde, Dimovski, Aleksandar, Brieghel, Christian, Lawless, Sarah, Meggendorfer, Manja, Brazdilova, Kamila, Ritgen, Matthias, Facco, Monica, Tresoldi, Cristina, Visentin, Andrea, Patriarca, Andrea, Catherwood, Mark, Bonello, Lisa, Sudarikov, Andrey, Vanura, Katrina, Roumelioti, Maria, Francova, Hana Skuhrova, Moysiadis, Theodoros, Veronese, Silvio, Giannopoulos, Krzysztof, Mansouri, Larry, Karan-Đurašević, Teodora, Sandaltzopoulos, Raphael, Bodor, Csaba, Fais, Franco, Kater, Arnon, Panovska, Irina, Rossi, Davide, Alshemmari, Salem, Panagiotidis, Panagiotis, Costeas, Paul, Espinet, Blanca, Antić, Darko, Foroni, Letizia, Montillo, Marco, Trentin, Livio, Stavroyianni, Niki, Gaidano, Gianluca, di Celle, Paola Francia, Niemann, Carsten, Campo, Elias, Anagnostopoulos, Achilles, Pott, Christiane, Fischer, Kirsten, Hallek, Michael, Oscier, David, Stilgenbauer, Stephan, Haferlach, Claudia, Jelinek, Diane, Chiorazzi, Nicholas, Pospisilova, Sarka, Lefranc, Marie-Paule, Kossida, Sofia, Langerak, Anton W., Belessi, Chrysoula, Davi, Frederic, Rosenquist, Richard, Ghia, Paolo, Stamatopoulos, Kostas, "Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL" in Blood, 137, no. 10 (2021):1365-1376, https://doi.org/10.1182/blood.2020007039 . .